Biomarkers in the Diagnosis and Prediction of Medication Response in Depression and the Role of Nutraceuticals.

Depression continues to be a significant and growing public health concern. In clinical practice, it involves a clinical diagnosis. There is currently no defined or agreed upon biomarker/s for depression that can be readily tested. A biomarker is defined as a biological indicator of normal physiological processes, pathogenic processes, or pharmacological responses to a therapeutic intervention that can be objectively measured and evaluated. Thus, as there is no such marker for depression, there is no objective measure of depression in clinical practice. The discovery of such a biomarker/s would greatly assist clinical practice and potentially lead to an earlier diagnosis of depression and therefore treatment. A biomarker for depression may also assist in determining response to medication. This is of particular importance as not all patients prescribed with medication will respond, which is referred to as medication resistance. The advent of pharmacogenomics in recent years holds promise to target treatment in depression, particularly in cases of medication resistance. The role of pharmacogenomics in routine depression management within clinical practice remains to be fully established. Equally so, the use of pharmaceutical grade nutrients known as nutraceuticals in the treatment of depression in the clinical practice setting is largely unknown, albeit frequently self-prescribed by patients. Whether nutraceuticals have a role in not only depression treatment but also in potentially modifying the biomarkers of depression has yet to be proven. The aim of this review is to highlight the potential biomarkers for the diagnosis, prediction, and medication response of depression.

Immunological Landscapes in Lung Transplantation: Insights from T Cell Profiling in BAL and PBMC.

Lung transplant recipients frequently encounter immune-related complications, including chronic lung allograft dysfunction (CLAD). Monitoring immune cells within the lung microenvironment is pivotal for optimizing post-transplant outcomes. This study examined the proportion of T cell subsets in paired bronchoalveolar lavage (BAL) and peripheral PBMC comparing healthy (n = 4) and lung transplantation patients (n = 6, no CLAD and n = 14 CLAD) using 14-color flow cytometry. CD4+ T cell proportions were reduced in CD3 cells in both PBMC and BAL, and positive correlations were discerned between T cell populations in peripheral PBMC and BAL, suggesting the prospect of employing less invasive PBMC sampling as a means of monitoring lung T cells. Furthermore, regulatory T cells (Tregs) were enriched in BAL when compared to peripheral PBMC for transplant recipients. A parallel positive correlation emerged between Treg proportions in BAL and peripheral PBMC, underscoring potential avenues for monitoring lung Tregs. Finally, the most promising biomarker was the Teff (CD8+Granzyme B+)-Treg ratio, which was higher in both the PBMC and BAL of transplant recipients compared to healthy individuals, and increased in the patients with CLAD compared to no CLAD and healthy patients. Conclusions: Distinct T cell profiles in BAL and peripheral PBMC underscore the significance of localized immune monitoring in lung transplantation. The Teff (CD8+granzyme B+)-Treg ratio, particularly within the context of CLAD, emerges as a promising blood and BAL biomarker reflective of inflammation and transplant-related complications. These findings emphasize the imperative need for personalized immune monitoring strategies that tailored to address the unique immunological milieu in post-transplant lungs.

Single-Cell Profiling of Cells in the Lung of a Patient with Chronic Hypersensitivity Pneumonitis Reveals Inflammatory Niche with Abundant CD39+ T Cells with Functional ATPase Phenotype: A Case Study.

This study investigated immune cell characteristics in chronic hypersensitivity pneumonitis (HP), focusing on CD39-expressing cells' impact on inflammation and tissue remodelling. Lung tissue from an HP patient was analysed using single-cell transcriptomics, flow cytometry, and gene expression profiling. The tissue revealed diverse cell types like macrophages, T cells, fibroblasts, and regulatory T cells (Tregs). CD39-expressing Tregs exhibited heightened ATP hydrolysis capacity and regulatory gene expression. CD39hi cells displayed markers of both Tregs and proinflammatory Th17 cells, suggesting transitional properties. Communication networks involving molecules like SPP1, collagen, CSF1, and IL-1ß were identified, hinting at interactions between cell types in HP pathogenesis. This research provides insights into the immune response and cell interactions in chronic HP. CD39-expressing cells dual nature as Tregs and Th17 cells suggests a role in modulating lung inflammation, potentially affecting disease progression. These findings lay the groundwork for further research, underscoring CD39-expressing cells as potential therapeutic targets in HP.

MicroRNAs involved in human skin burns, wound healing and scarring.

MicroRNAs are small, non-coding RNAs that regulate gene expression, and consequently protein synthesis. Downregulation and upregulation of miRNAs and their corresponding genes can alter cell apoptosis, proliferation, migration and fibroproliferative responses following a thermal injury. This review summarises the evidence for altered human miRNA expression post-burn, and during wound healing and scarring. In addition, the most relevant miRNA targets and their roles in potential pathways are described. Previous studies using molecular techniques have identified 197 miRNAs associated with human wound healing, burn wound healing and scarring. Five miRNAs alter the expression of fibroproliferative markers, proliferation and migration of fibroblasts and keratinocytes post-burn: hsa-miR-21 and hsa-miR-31 are increased after wounding, and hsa-miR-23b, hsa-miR-200b and hsa-let-7c are decreased. Four of these five miRNAs are associated with the TGF-ß pathway. In the future, large scale, in vivo, longitudinal human studies utilising a range of cell types, ethnicity and clinical healing outcomes are fundamental to identify burn wound healing and scarring specific markers. A comprehensive understanding of the underlying pathways will facilitate the development of clinical diagnostic or prognostic tools for better scar management and the identification of novel treatment targets for improved healing outcomes in burn patients.

Pyrroles as a Potential Biomarker for Oxidative Stress Disorders.

Redox imbalance or oxidative stress that results from both environmental and genetic factors is observed in patients with schizophrenia. Therefore, identifying markers of oxidative stress in the early stages of psychosis and using antioxidant treatments as an adjuvant to antipsychotics has important implications. The reaction of p-N,N-dimethylaminobenzaldehyde (DMAB) with pyrrole moieties has been well studied for well over a century for use as a marker of oxidative stress dysregulation. Throughout this time, pyrroles have been investigated with varying veracity in urine extracts to identify elevated levels in patients diagnosed with schizophrenia. Since the 1960's, various claims have been made with respect to what causes the colour change when DMAB is added to urine extracts. Whilst the substances from this reaction have not been fully elucidated, an objective look at most studies indicates that urobilinogen is likely to be one them. Urobilinogen has also been identified as a major interferent in our results. Both pyrroles and urobilinogen condense the DMAB reaction system (form condensation products) and are quite different. The urobilinogen detected in urine forms when gut microflora chemically reduces the bilirubin content of bile acids. In comparison, evidence suggests that the pyrrole fraction originates from the fragmentation of regulatory haem by reactive oxygen species (ROS) such as hydrogen peroxide and super and nitrous oxides. Clinical studies in our laboratories have established that pyrroles as a urine biomarker have specificity in detecting schizophrenia; however, caution must be applied as the readings are subject to interference by other DMAB active compounds that are present, such as urobilinogen. This review highlights the initial chemistry in isolating pyrroles and provides recommendations for standardised laboratory testing to ensure pyrroles are correctly measured and distinguished from other by-products.

Markers of rejection of a lung allograft: state of the art.

Chronic lung allograft dysfunction (CLAD) affects approximately 50% of all lung transplant recipients by 5 post-operative years and is the leading cause of death in lung transplant recipients. Early CLAD diagnosis or ideally prediction of CLAD is essential to enable early intervention before significant lung injury occurs. New technologies have emerged to facilitate biomarker discovery, including epigenetic modification and single-cell RNA sequencing. This review examines new and existing technologies for biomarker discovery and the current state of research on biomarkers for identifying lung transplant rejection.

An Exploratory Study Demonstrating That Salivary Cytokine Profiles Are Altered in Children With Small Area Thermal Injury.

Serum can be used to investigate changes in cytokine concentration following burn injury in children; however, for children receiving treatment in an outpatient setting, blood is not routinely collected and therefore cannot be used for monitoring. The aim of this study was to investigate the use of saliva as a noninvasive tool for predicting burn outcomes by measuring the concentration of salivary cytokines in children with small area burns. A multiplex cytokine assay was used to measure 17 cytokines in the saliva of pediatric patients with burns (n = 20) and healthy controls (n = 20). After the removal of cytokines that had >30% of samples below the assay lower detection limit, six cytokines including IL-1ß, IL-4, IL-7, IL-8, MCP-1, and TNFα were analyzed for association with burns. IL-1ß and IL-4 were found to be significantly elevated in the pediatric burn patients compared to healthy controls. Interestingly, IL-1ß was also significantly elevated in scald burns, compared to contact burns. In addition, biologically meaningful differences in cytokine concentration were identified in patients with different burn characteristics, which warrant further investigation. This exploratory study provides evidence that cytokines can be detected in the saliva of children and that salivary cytokine profiles differ between healthy controls and children with burns. Overall, this study demonstrates the value of saliva for the investigation of cytokines and its potential application in pediatric diagnostics, specifically in situations where blood collection is not appropriate.

Investigation of C-reactive protein and AIM2 methylation as a marker for PTSD in Australian Vietnam veterans.

Chronic inflammation is a key factor in symptomology and comorbidities of post-traumatic stress disorder (PTSD). Levels of a proinflammatory marker, C-reactive protein (CRP) are increased in individuals with PTSD but it is not clear if this is due to trauma exposure or PTSD. Our study aimed to assess the relationship between serum CRP levels, CRP SNPs, methylation, mRNA expression and PTSD in a homogenous trauma exposed Australian Vietnam veteran cohort. We hypothesized that decreased DNA methylation would be associated with increased gene expression and increased peripheral CRP levels in PTSD patients and that this would be independent of trauma. Participants were 299 Vietnam veterans who had all been exposed to trauma and approximately half were diagnosed with PTSD. We observed higher levels of serum CRP in the PTSD group compared to the non-PTSD group but after controlling for BMI and triglycerides the association did not remain significant. No association was found between CRP SNPs and PTSD or CRP levels. Absent in Melanoma 2 (AIM2) which is a mediator of inflammatory response and a determinant of CRP levels was analysed for DNA methylation and mRNA expression. We observed a trend level association between PTSD and AIM2 methylation after controlling for age, smoking, triglycerides, BMI and cell types. There was no significant interaction between PTSD and CRP levels on AIM2 methylation after controlling for covariates. We observed that as AIM2 methylation levels decreased, AIM2 mRNA expression increased. Elevated CRP levels were associated with AIM2 mRNA in the trauma exposed cohort but there was no significant interaction effect with PTSD. Our results could not confirm that CRP is a marker of PTSD independent of trauma in this group of older veterans. CRP may be a broad marker of disease risk, or a marker of PTSD in younger cohorts than those in this study.

Examining Individual and Synergistic Contributions of PTSD and Genetics to Blood Pressure: A Trans-Ethnic Meta-Analysis.

Growing research suggests that posttraumatic stress disorder (PTSD) may be a risk factor for poor cardiovascular health, and yet our understanding of who might be at greatest risk of adverse cardiovascular outcomes after trauma is limited. In this study, we conducted the first examination of the individual and synergistic contributions of PTSD symptoms and blood pressure genetics to continuous blood pressure levels. We harnessed the power of the Psychiatric Genomics Consortium-PTSD Physical Health Working Group and investigated these associations across 11 studies of 72,224 trauma-exposed individuals of European (n = 70,870) and African (n = 1,354) ancestry. Genetic contributions to blood pressure were modeled via polygenic scores (PGS) for systolic blood pressure (SBP) and diastolic blood pressure (DBP) that were derived from a prior trans-ethnic blood pressure genome-wide association study (GWAS). Results of trans-ethnic meta-analyses revealed significant main effects of the PGS on blood pressure levels [SBP: ß = 2.83, standard error (SE) = 0.06, p < 1E-20; DBP: ß = 1.32, SE = 0.04, p < 1E-20]. Significant main effects of PTSD symptoms were also detected for SBP and DBP in trans-ethnic meta-analyses, though there was significant heterogeneity in these results. When including data from the largest contributing study - United Kingdom Biobank - PTSD symptoms were negatively associated with SBP levels (ß = -1.46, SE = 0.44, p = 9.8E-4) and positively associated with DBP levels (ß = 0.70, SE = 0.26, p = 8.1E-3). However, when excluding the United Kingdom Biobank cohort in trans-ethnic meta-analyses, there was a nominally significant positive association between PTSD symptoms and SBP levels (ß = 2.81, SE = 1.13, p = 0.01); no significant association was observed for DBP (ß = 0.43, SE = 0.78, p = 0.58). Blood pressure PGS did not significantly moderate the associations between PTSD symptoms and blood pressure levels in meta-analyses. Additional research is needed to better understand the extent to which PTSD is associated with high blood pressure and how genetic as well as contextual factors may play a role in influencing cardiovascular risk.

A review of potential biomarkers for assessing physical and psychological trauma in paediatric burns.

Biological markers that evaluate physical healing as well as psychological impact of a burn are essential for effective treatment of paediatric burns. The objective of this review is to summarize the evidence supporting the use of biomarkers in children with burns. An extensive review of the literature was performed using PubMed. A total of 59 biomarkers were identified relating to burn presence, specifically relating to processes involved in inflammation, wound healing, growth and metabolism. In addition, biomarkers involved in the stress response cascade following a burn trauma were also identified. Although many biomarkers have been identified that are potentially associated with burn-related physical and psychological trauma, an understanding of burn biology is still lacking in children. We propose that future research in the field of children's burns should be conducted using broad screening methods for identifying potential biomarkers, examine the biological interactions of different biomarkers, utilize child-appropriate biological fluids such as urine or saliva, and include a range of different severity burns. Through further research, the biological response to burn injury may be fully realized and clinically relevant diagnostic tests and treatment therapies utilizing these biomarkers could be developed, for the improvement of healing outcomes in paediatric burn patients.

NLRP3 is associated with coronary artery disease in Vietnam veterans.

BACKGROUND: Previous studies have established that coronary artery disease is associated with excess inflammation. These studies have shown an elevation of both pro and anti-inflammatory cytokines in sufferers of coronary artery disease. There is increasing interest in the role played by the inflammasome Nod Like Receptor family pyrin domain containing 3 (NLRP3) in the aetiology of coronary artery disease. Increased severity of coronary artery disease correlates with higher levels of expression of NLRP3. Does NLRP3 polymorphisms play a role in the aetiology of coronary artery disease? METHOD: In a cohort of Vietnam War (n-299) veterans who have been previously exposed to trauma, NLRP3 polymorphisms were analysed for association with coronary calcium scores using analyses of variance. Independent t-test was used to analyse genotypes. In samples with a small representation of minor homozygotes, genotypes were combined and analysed using independent t-test. If any of the genotype analysis suggested the potential for a dominant or a recessive model the model was further explored. Hardy-Weinberg Equilibrium was calculated using Hardy-Weinberg equilibrium calculator including analysis for ascertainment bias. RESULTS: The NLRP3 polymorphism, rs10159239 was significantly associated (p = 0.001) with a higher raised coronary calcium score. The Single Nucleotide Polymorphism rs10159239 was examined by logistic regression with known risk factors for Coronary artery disease and remained significant (0.035). This is the first time rs10159239 A-allele has been associated with raised coronary calcium score. CONCLUSIONS: This is the first time rs10159239 A-allele has been associated with raised coronary calcium score. Further research is needed to replicate our results in larger well-characterised cohorts.

DNA methylation from germline cells in veterans with PTSD.

In this study we investigated genome-wide sperm DNA methylation patterns in trauma-exposed Vietnam veterans. At the genome-wide level, we identified 3 CpG sites associated with PTSD in sperm including two intergenic and one CpG within the CCDC88C gene. Of those associated with PTSD in sperm at a nominal level, 1868 CpGs were also associated with PTSD in peripheral blood (5.6% overlap) including the RORA, CRHR1 and DOCK2 genes that have been previously implicated in PTSD. A total of 10 CpG sites were significantly associated with a reported history of a diagnosed mental health condition in children and reached genome-wide significance. CpGs associated with a history of a reported mental health condition in children were also enriched (90% of tested genes) for genes previously reported to be resistant to demethylation, making them strong candidates for transgenerational inheritance. In conclusion, our findings identify a unique sperm-specific DNA methylation pattern that is associated with PTSD.

Differential BDNF methylation in combat exposed veterans and the association with exercise.

Brain-derived neurotrophic factor (BDNF) gene is associated with increased risk of posttraumatic stress disorder (PTSD) and plays a role in neuroplasticity, cognition and memory. BDNF has strong potential as a therapeutic target as studies have shown that antidepressants, electroconvulsive treatment and exercise modulate BDNF expression and methylation. In this study we examined the role of BDNF methylation and expression in PTSD and the implications of exercise in mediating these effects. BDNF DNA methylation and gene expression analysis was performed in a sample of 96 male Vietnam veterans. Cases were combat-exposed veterans with current PTSD (n = 48) and controls were combat exposed veterans with no past or current PTSD diagnosis (n = 48). No association between BDNF mRNA and PTSD was identified. PTSD was associated with decreased methylation at three BDNF CpG sites (cg01546433 P = 0.004835; cg24650785 P = 0.000259 and cg002298481 P = 0.000672). Differential BDNF methylation was associated with exercise, with active exercise associated with lower methylation levels at three CpG sites (cg04481212 P = 0.005; cg01546433 P = 0.025 and cg00298481 P = 0.035). Given that exercise mediates BDNF action on cognitive plasticity, exercise may be a non-invasive, drug free option in the treatment of PTSD.

The inflammasome NLRP12 is associated with both depression and coronary artery disease in Vietnam veterans.

Several studies have established that Major depressive disorder is associated with excess inflammation with an elevation of both pro and anti-inflammatory cytokines in major depressive disorder. In addition, individuals with major depressive disorder are at higher risk of developing coronary artery disease. The role of innate immunity and NFκB-mediated inflammation in depression and its increased association with coronary artery disease is yet to be fully elucidated. Polymorphisms in the Nucleotide-Binding Oligomerization Domain, Leucine Rich Repeat and Pyrin Domain Containing 12 (NLRP12), are associated with depression and coronary artery disease in trauma exposed individuals. In a cohort of Vietnam War veterans (n = 299) NLRP12 polymorphisms were analysed for association with depression and coronary calcium scores. The NLRP12 polymorphism, rs34436714 was associated with a higher DASS21 Score for depression (p = 0.037). NLRP12 polymorphisms rs34971363 and rs6509825 (p = 0.022 and p = 0.020) were associated with raised coronary calcium score. To our knowledge, this is the first time rs34436714 has been investigated in Vietnam veterans identifying AC as a risk genotype for depression in Caucasian cohorts. It is also the first time the rs34971363 (CG) and rs6509825 (CT) genotype have been associated with raised coronary calcium score.

Transcriptome analysis reveals novel genes and immune networks dysregulated in veterans with PTSD.

BACKGROUND: Posttraumatic stress disorder (PTSD) is a serious condition that emerges following trauma exposure and involves long-lasting psychological suffering and health-issues. Uncovering critical genes and molecular networks is essential to understanding the biology of the disorder. We performed a genome-wide scan to identify transcriptome signatures of PTSD. METHODS: Genome-wide peripheral blood transcriptomic data from 380 service personnel were investigated. This included a discovery sample of 96 Australian Vietnam War veterans and two independent pre and post-deployment replication samples of U.S. Marines (N = 188 and N = 96). RESULTS: A total of 60 transcripts were differentially expressed between veterans with and without PTSD, surviving Bonferroni multiple testing correction. Genes within the cytokine-cytokine receptor interaction, Jak-STAT signaling and Toll-like receptor signaling pathways were enriched. For 49% of the genes, gene expression changes were also accompanied by DNA methylation changes. Using replication data from two U.S. Marine cohorts, we observed that of the differentially expressed genes, 71% genes also showed significant gene expression changes between pre and post-deployment. Weighted gene co-expression networks revealed two modules of genes associated with PTSD. The first module (67 genes, p-value = 6e-4) was enriched for genes within the 11p13 locus including BDNF. The second module (266 genes, p-value = 0.01) was enriched for genes in 17q11 including SLC6A4, STAT5A and STAT5B. CONCLUSIONS: We identified novel transcriptomic loci and biological pathways for PTSD in service personnel. Network analysis revealed enrichment of loci harboring key candidate genes in PTSD. These findings highlight the role of transcriptional biomarkers in the molecular etiology of PTSD.

Detailed Polysomnography in Australian Vietnam Veterans With and Without Posttraumatic Stress Disorder.

STUDY OBJECTIVES: Recent results from the PTSD Initiative, a cross-sectional cohort study in Australian Vietnam veterans (VV) with and without posttraumatic stress disorder (PTSD), demonstrated an increased prevalence of self-reported sleep disturbances in those with PTSD. This study aimed to objectively assess the prevalence of sleep disorders in the same cohort using detailed polysomnography (PSG). METHODS: Participants from the PTSD Initiative were recruited to undergo PSG. PTSD status was determined with the Clinician Administered PTSD Scale for DSM-5 (CAPS-5). Subjective sleep information was attained via structured questionnaires. Data from single night PSG were compared between trauma-exposed VV with and without PTSD. RESULTS: A total of 74 trauma-exposed male VV (40 with PTSD) underwent PSG (prospective n = 59, retrospective n = 15). All PSG parameters were similar between groups. No difference was seen in PSG-diagnosed obstructive sleep apnea (OSA) or periodic limb movements of sleep (PLMS). VV with PTSD showed a trend toward increased duration of sleep with oxygen saturations < 90% (10% versus 1.8%; P = .07). VV with PTSD reported increased sleep onset latency (42.4 versus 13.3 minutes; P < .01); were less likely to report sleeping well (32.5% versus 67.5%; P < .01); had higher OSA risk using Berlin Questionnaire (BQ) (70% versus 38.2%; P < .01); and had higher rates of partner-reported limb movements (56.4% versus 17.6%; P < .01). No association between PSG-diagnosed OSA and PTSD severity was evident. CONCLUSIONS: In Australian VV with and without PTSD, no difference was seen across all PSG parameters including the diagnosis and severity of OSA and PLMS. However, VV with PTSD demonstrated an increased perception of sleep disturbances.

The association between post-traumatic stress disorder and coronary artery disease: a meta-analysis.

OBJECTIVES: There are some psychosocial factors that have similar importance to biological factors in the genesis of coronary diseases. However, reasons for high rates of coronary heart disease in individuals with post-traumatic stress disorder (PTSD) are yet to be fully elucidated. Using a meta-analysis, we investigated the longitudinal relationship between PTSD and coronary heart disease (CHD) as an independent factor in the aetiology of CHD. METHODS: The databases of Medline, EBSCOhost and Psychoinfo were electronically searched for relevant articles. RESULTS: The pooled hazard ratio (HR) for the magnitude of the relationship between PTSD and CHD was an HR of 1.61, and p-value of p < 0.0005, 95% confidence interval (CI) [1.46-1.77] before adjustment for depression in nine studies ( N = 151,144) that met inclusion criteria. The HR estimates for the seven depression-adjusted estimates was 1.46, and a p-value of p < 0.0005, 95% CI[0.26-1.69]. CONCLUSIONS: This study demonstrates an association between CHD and PTSD.

Accelerated DNA methylation aging and increased resilience in veterans: The biological cost for soldiering on.

Accelerated epigenetic aging, the difference between the DNA methylation-predicted age (DNAm age) and the chronological age, is associated with a myriad of diseases. This study investigates the relationship between epigenetic aging and risk and protective factors of PTSD. Genome-wide DNA methylation analysis was performed in 211 individuals including combat-exposed Australian veterans (discovery cohort, n = 96 males) and trauma-exposed civilian males from the Grady Trauma Project (replication cohort, n = 115 males). Primary measures included the Clinician Administered PTSD Scale for DSM-5 and the Connor-Davidson Resilience Scale (CD-RISC). DNAm age prediction was performed using the validated epigenetic clock calculator. Veterans with PTSD had increased PTSD symptom severity (P-value = 3.75 × 10-34) and lower CD-RISC scores (P-value = 7.5 × 10-8) than veterans without PTSD. DNAm age was significantly correlated with the chronological age (P-value = 3.3 × 10-6), but DNAm age acceleration was not different between the PTSD and non-PTSD groups (P-value = 0.24). Evaluating potential protective factors, we found that DNAm age acceleration was significantly associated with CD-RISC resilience scores in veterans with PTSD, these results remained significant after multiple testing correction (P-value = 0.023; r = 0.32). This finding was also replicated in an independent trauma-exposed civilian cohort (P-value = 0.02; r = 0.23). Post-hoc factor analyses revealed that this association was likely driven by "self-efficacy" items within the CD-RISC (P-value = 0.015; r = 0.35). These results suggest that among individuals already suffering from PTSD, some aspects of increased resilience might come at a biological cost.

Correlation between interferon γ and interleukin 6 with PTSD and resilience.

Posttraumatic Stress Disorder (PTSD) is a debilitating psychiatric disorder with decreased general health prognosis and increased mortality. Inflammation has been hypothesised to be a link between PTSD and the most common co-morbid medical disorders. However, the relationship between inflammation and PTSD is not clear. Individual inflammatory markers have shown variable associations with PTSD. This study investigates the correlations between serum cytokines, PTSD and resilience in a cohort of Caucasian Vietnam combat veterans (n = 299). After correction for multiple testing, PTSD severity was correlated with small but significant decreases in interleukin 6 and interferon γ (p = 0.004, p = 0.013, respectively) whereas resilience was correlated with increased levels of interleukin 6 and interferon γ (p = 0.023; p = 0.007, respectively). Analyses of sub-symptoms of PTSD revealed that mood and arousal symptoms showed the most significant effect on interleukin 6 and interferon γ. More research is needed to further elucidate the mechanisms underlying the relationship between cytokine levels, PTSD sub-symptoms and trauma outcomes to improve the knowledge base of differences in trauma response and the biological system.

PTSD symptoms associated with myocardial infarction: practical clinical implications.

OBJECTIVES: Several studies have demonstrated a link between post-traumatic stress disorder and myocardial infarction. We aim to determine what phenotypic features or symptom profile associated with cardiovascular disease may help with early detection and intervention. METHODS: This is a cross-sectional study. The study population comprises trauma-exposed Vietnam War veterans. RESULTS: Variables significantly associated with myocardial infarction from the bivariate analysis were avoidance memories, avoidance reminders and sleep disturbance. These variables were put into a logistic regression with known risk factors for myocardial infarction. Only sleep disturbance retained its effect, with a p-value of 0.015. CONCLUSIONS: It is concluded that sleep disturbance may be a modifiable risk factor in the treatment and prevention of myocardial infarction.